Neurosurgery notes/Trauma/Management of trauma/Non surgical/Head injury ICP management/Hyperosmolar therapy/Mannitol

Mannitol

View Details
logo
Parent item
Hyperosmolar therapy
  • Indications:
    • Evidence of intracranial hypertension
    • Evidence of mass effect (focal deficit, e.g. hemiparesis)
    • Sudden deterioration prior to CT (including pupillary dilatation)
    • After CT, if a lesion that is associated with increased ICP is identified
    • After CT, if going to O.R.
    • To assess “salvageability”: in patient with no evidence of brainstem function, look for return of brainstem reflexes
  • Contraindications:
    • Prophylactic administration is not recommended due to its volume-depleting effect. Use only for appropriate indications (see above)
    • Hypotension or hypovolemia:
      • Hypotension can negatively influence outcome.
        • Therefore, when intracranial hypertension (IC-HTN) is present,
          • First utilize sedation and/or paralysis, and CSF drainage.
          • If further measures are needed, fluid resuscitate the patient before administering mannitol.
            • Use hyperventilation in hypovolemic patients until mannitol can be given
    • Relative contraindication:
      • Mannitol may slightly impede normal coagulation
    • CHF:
      • Before causing diuresis, mannitol transiently increases intravascular volume.
      • Use with caution in CHF, may need to pre-treat with furosemide (Lasix®)
    • Established anuria due to severe renal disease
    • Pulmonary congestion and frank pulmonary oedema
    • Active internal bleeding
    • Severe dehydration
    • Hypersensitivity to mannitol
  • No RTC has been conducted to show the benefits of mannitol over placebo
  • Mechanism of action
    • Still controversial, but probably includes some combination of the following
    • Lowering ICP
      • Haemodynamic effects:
        • Occurs first (Within a few minutes)
        • Most marked in patients with CPP< 70mm Hg
        • Mannitol bonus pulls water from cells (including RBC) into plasma → Increase plasma volume (reduces haematocrit) → reduce blood viscosity (improved rheology) → increases cerebral blood flow → auto regulation then causes vasoconstriction to reduce cerebral blood flow back to normal → this reduction in cerebral blood flow decreases ICP
        • Due to the presence of the haemodynamic effects, mannitol still works without having an intact BBB
      • Osmotic effect:
        • Requires an intact BBB to set up an osmotic gradient
        • Increased serum tonicity draws oedema fluid from cerebral parenchyma.
        • Takes 15–30 minutes until gradients are established.
        • Effect lasts 1.5–6 hrs, depending on the clinical condition
      • Diuretic effect:
    • Possible free radical scavenging
  • With bolus administration,
    • Onset of ICP lowering effect occurs in 1–5minutes;
    • Peaks at 20– 60 minutes.
  • Bolus mannitol can lead to
    • 10% ICP reduction among 86% of patients with intact autoregulation,
    • 10% ICP reduction in only 35% of patients with impaired autoregulation (Muizelaar et al., 1984).
      • When autoregulation is lost osmotic agents may increase CBF without compensatory vasoconstriction and thus the desired reduction in ICP may not be achieved.
  • ℞:
    • An initial dose of 1 g/kg should be given over 30 minutes.
    • When long-term reduction of ICP is intended, the infusion time should be lengthened to 60 minutes and the dose reduced (e.g. 0.25–0.5 gm/kg q 6 hrs).
    • A large previous dose reduces the effectiveness of subsequent doses; thus it is desirable to use the smallest effective dose (small frequent doses may be preferable, e.g. 0.25 mg/kg q 2–3 hrs; also results in fewer peaks as mannitol “troughs” are smoothed out).
    • Keep patient euvolemic to slightly hypervolemic
    • May “alternate” with: furosemide (Lasix®)
      • Adult 10–20mg IV q 6 hrs PRN ICP > 22
      • Paeds: 1mg/kg, 6mg max IV q 6 hrs PRN ICP > 22
    • If IC-HTN persists and serum osmolarity is < 320 mOsm/L,
      • Increase mannitol up to 1 gm/kg, and shorten the dosing interval
    • If ICP remains refractory to mannitol,
      • Consider hypertonic saline, either continuous 3% saline infusion or as bolus of 10–20ml of 23.4% saline (D/C after ≈ 72 hours to avoid rebound oedema)
    • Hold osmotic therapy if serum osmolarity is ≥ 320 mOsm/L (higher tonicity may have no advantage and risks renal dysfunction; see below) or SBP<100
  • Titrating to ICP (instead of dosing at regular intervals) results in less mannitol being given.
  • The effectiveness of mannitol may be synergistically enhanced when combined with the use of loop acting diuretics (e.g. furosemide), and alternating these medications has been suggested.
  • Cautions with mannitol
    • BBB is compromised → mannitol can that has crossed the BBB may draw fluid into the CNS (this may be minimized by repeated bolus administration vs. continuous infusion) → aggravate vasogenic cerebral oedema.
      • When it is time to withdraw mannitol, it should be tapered to prevent ICP rebound
    • Corticosteroids + phenytoin + mannitol may cause hyperosmolar nonketotic state with high mortality
    • Excessively vigorous bolus administration may → HTN and if autoregulation is defective → increased CBF which may promote herniation rather than prevent it
    • High doses of mannitol carries the risk of acute renal failure (acute tubular necrosis), especially in the following:
      • Serum osmolarity > 320 mOsm/L,
      • Use of other potentially nephrotoxic drugs, sepsis, pre-existing renal disease
    • Large doses prevents diagnosing DI by use of urinary osmols or SG
    • Because it may further increase CBF, the use of mannitol may be deleterious when IC-HTN is due to hyperemia
    • At sub zero temp can crystalize